Devices and methods for disruption and removal of luminal occlusions

ABSTRACT

The subject invention pertains to an elastic sheath, device, and methods for disrupting and/or removing occlusive material from lumens, particularly biological lumens, such as the vasculature, ureter, urethra, fallopian tubes, bile duct, intestines, and the like. The subject invention provides for effective disruption and removal of occlusive material, such as a thrombus, from the body lumen with minimal risk of injury to the lumen wall. Advantageously, the invention can be used to achieve a high degree of removal while minimizing the amount of occlusive material that is released into the body lumen. The subject invention further pertains to methods for disrupting and removing occlusive material from a biological lumen. In another aspect, the present invention concerns a device useful as an in vitro model of luminal occlusion and methods for using the device to test the efficacy of devices and methods for treating luminal occlusions.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a divisional of U.S. patent application Ser.No. 10/844,737, filed on May 12, 2004, which claims the benefit of U.S.Provisional Application Ser. No. 60/470,067, filed May 12, 2003. Each ofthese applications is incorporated by reference herein in its entirety,including any figures, tables, nucleic acid sequences, amino acidsequences, or drawings.

BACKGROUND OF THE INVENTION

The blockage of human arteries can lead to a variety of serious medicalcomplications. Arterial blockages reduce blood flow through the affectedartery and may result in damage to the tissue that is relying upon theblood's supply of oxygen (ischemia). For example, if the blockage is inan artery that supplies blood to the heart itself, a heart attack mayresult.

Thrombosis and atherosclerosis are common ailments that result from thedeposition of thrombus on the walls of blood vessels. When such depositsharden, they are commonly referred to as plaque. These plaque depositsoccur commonly in blood vessels that feed the brain, heart, and limbs ofthe human body. Stasis, incompetent valves, and trauma in the venouscirculation are common causes of thrombosis, which can often manifest asa deep vein thrombosis in the peripheral vasculature. When such depositsbuild-up in localized regions of the blood vessel, they can restrictblood flow and cause a serious health risk.

In addition to forming in the natural vasculature, thrombosis is aserious problem in “artificial” blood vessels, particularly inperipheral femoral-popliteal and coronary bypass grafts and dialysisaccess grafts and fistulas. The creation of such artificial bloodvessels requires anastomotic attachment at one or more locations in thevasculature. Such sites are particularly susceptible to thrombusformation due to narrowing caused by intimal hyperplasia, and thrombusformation at these sites is a frequent cause of failure of the implantedgraft or fistula. The arterio-venous grafts and fistulas that are usedfor dialysis access are significantly compromised by thrombosis at thesites of anastomotic attachment and elsewhere. Thrombosis often occursto such an extent that the graft needs to be replaced within a few yearsor even a few months.

A variety of methods have been developed for treating thrombosis andatherosclerosis in the coronary and peripheral vasculature as well as inimplanted grafts and fistulas. Such techniques include pharmacologicthrombolytic therapy, given either intravenously or intra-arterially(Hacke W. et al., JAMA, 274:1017-1025, 1995; del Zoppo G. J. et al.,Stroke, 29:4-11, 1998), surgical procedures, such as coronary arterybypass grafting, and minimally invasive procedures, such as angioplastyatherectomy, transmyocardial and revascularization. In particular, avariety of techniques generally referred to as “thrombectomy” have beendeveloped. Thrombectomy generally refers to procedures for the removalof relatively soft thrombus and clot from vasculature. Removal isusually achieved by mechanically disrupting the clot, and can optionallyinclude the administration of thrombolytic agents. The disruptedthrombus or clot is then withdrawn through a catheter, typically with avacuum or mechanical transport device.

Thrombectomy generally differs from angioplasty and atherectomy in thetype of occlusive material that is being treated and in the level ofcare taken to avoid damage to the blood vessel wall. The materialremoved in most thrombectomy procedures is relatively soft, such as theclot formed in deep vein thrombosis, and is usually not hardened plaqueof the type treated by angioplasty in the coronary vasculature.Moreover, it is usually an objective of thrombectomy procedures to haveminimum or no deleterious interaction with the blood vessel wall.Ideally, the clot will be disrupted and pulled away from the bloodvessel wall with no harmful effect on the wall itself.

While successful thrombectomy procedures have been achieved, most haverequired compromise between the competing objectives of removing thethrombosis and minimizing injury to the blood vessel wall. While moreaggressive thrombectomy procedures employ rotating blades that can bevery effective at thrombus removal, they present a significant risk ofinjury to the blood vessel wall. Alternatively, those procedures thatrely primarily on vacuum extraction together with minimum disruption ofthe thrombus, often fail to achieve sufficient thrombus removal.

U.S. Pat. No. 5,904,698 describes a catheter having an expandable meshwith a blade or electrode for shearing obstructive material, whichpenetrates the mesh when the mesh is expanded in a blood vessel. Othercatheters having expandable meshes, cages, and/or shearing elements aredescribed in U.S. Pat. Nos. 5,972,019; 5,954,737; 5,795,322; 5,766,191;5,556,408; 5,501,408; 5,330,484; 5,116,352; and 5,410,093; and WO96/01591. Catheters with helical blades and/or Archimedes screws fordisrupting and/or transporting clot and thrombus are described in U.S.Pat. Nos. 5,947,985; 5,695,501; 5,681,335; 5,569,277; 5,569,275;5,334,211; and 5,226,909. Other catheters of interest for performingthrombectomy and other procedures are described in U.S. Pat. Nos.5,928,186; 5,695,507; 5,423,799; 5,419,774; 4,762,130; 4,646,736; and4,621,636. Techniques for performing thrombectomy are described inSharafudin et al. (JVIR 8:911-921, 1997) and Schmitz-Rode et al.(Radiology 180:135-137, 1991).

One of the problems with many of these devices, however, is thatparticulate matter (e.g., thrombus, atheroma, or other embolic orocclusive material) may be released from the wall of the vessel duringthe procedure. If such particulate matter travels downstream, it maybecome lodged or otherwise harm the patient. For example, ischemicstroke may occur when such emboli are released in the carotid orcerebral arteries and travel to the patient's brain. To prevent orminimize damage from emboli, vascular filters have been suggested thatare typically disposed on a device such as a catheter, guidewire, orsheath. These devices may be introduced within a blood vessel downstreamof a location being treated, and the filter on the device deployedacross the vessel to capture embolic material released during theprocedure. Upon completion of the procedure, the filter may becollapsed, trapping emboli therein, and then the device may be removedfrom the patient. Catheters having expandable filters at their distalends are described in U.S. Pat. No. 4,928,858 and PCT publications WO99/44542 and WO 99/44510.

The United States Food and Drug Administration (FDA) has approved atotal of eight mechanical thrombectomy devices (MTDs) for use inthrombosed hemodialysis grafts (Kasirajan K. et al, J. Vase. Interv.Radiol, 2001, 12:405-411). Generally, the approved MTDs can beclassified into two categories: (i) mechanical lysis only(non-aspirating) devices and (ii) mechanical and aspirating devices. TheAMPLATZ thrombectomy device (CLOT BUSTER; MICROVENA, White Bear Lake,Minn.), ARROW-TREROTOLA PTD (ARROW INTERNATIONAL, Reading, Pa.), andCASTANEDA OVER-THE-WIRE BRUSH (MICRO THERAPEUTICS, Aliso Viego, Calif.)are categorized mechanical non-aspirating devices and ANGIOJET (POSSISMEDICAL; Minneapolis Minn.), GELBFISH-ENDOVAC (BOSTONSCIENTIFIC/MEDI-TECH, Brooklyn, N.Y.), HYDROLYSER(CORDIS, Miami, Fla.),OASIS (BOSTON SCIENTIFIC/MEDI-TECH, Watertown, Mass.) are categorizedunder mechanical aspirating devices. The ANGIOJET LF140 (POSSIS MEDICAL,Minneapolis, Minn.) is the only FDA approved device for use inperipheral arterial occlusive disease. These devices are currently beingused or undergoing clinical evaluation for the treatment of acute andchronic limb-threatening ischemia.

Stroke is characterized by a sudden loss of blood supply to the brain,which results in loss of neurological function. Stroke is the thirdleading cause of death in the United States (150,000 cases per year) andthe leading cause of adult disability (“2002 Heart and StrokeStatistical Update”, American Heart Association, Dallas, Tex., 2001).Approximately 700,000 strokes occur annually in the U.S., accounting forcosts of over $26 billion/year for treatment and rehabilitation. Strokeis currently classified into two categories: hemorrhagic and ischemic.Ischemic stroke is the most common type and accounts for 85% of allstroke cases. Ischemic stroke (i.e., thromboembolic stroke) occurs whenarteries supplying blood to the brain are occluded by thrombus or otherembolic material (e.g., calcifications, cholesterol, plaque, etc.).

Current treatment modalities include pharmacologic thrombolytic therapy;however, all thrombolytic drugs are not indicated for all stroke victimsand are not effective for all thromboembolic occlusions. The treatmentof ischemic stroke patients with tissue plasminogen activator (tPA) iscurrently the only FDA approved treatment in the United States. However,tPA has been shown to benefit patients only if administered within a 3hour time window after the onset of neurological symptoms. Therefore, apoor success rate in treatment of stroke is observed. Moreover, the useof tPA is associated with a high risk of hemorrhage and cannot be givento all patients. Endovascular mechanical thrombolytic devices could beused to treat ischemic stroke patients less invasively and moreeffectively. Unfortunately, there currently exists no FDA approveddevice for ischemic stroke treatment. Mechanical thrombectomy devicesmay increase the risk of arterial performation, dissection, orendothelial injury, which can result in intracranial hemorrhage andworsening of neurological deficits, for example. Therefore, making suchdevices that will eliminate or even reduce these risks is an extremelychallenging task. For example, a device adapted to treat ischemic strokeshould be miniaturized to fit inside intracranial arteries, which arerelatively small (1 mm to 3.5 mm in diameter). Intracranial arteries arefragile and tortuous; therefore, the device should also be highlyflexible and maneuverable. The use of such devices, along with tPA, maybenefit patients by providing a quick recovery from ischemic stroke.

Preliminary studies on the safety, efficacy, and device limitations havespurred an interest in percutaneous techniques for thrombus debulking asstand-alone therapy or as an adjunct to pharmacologic thrombolysis. Thedevices have various mechanisms or combinations of mechanisms tooptimize thrombus removal. Efficacy of thrombus removal is balanced bythe propensity for vessel wall damage and distal embolization,especially for vessel wall-contact devices.

Therefore, there is a need for a device that is simple in design and ishighly maneuverable to permit navigation through various lumen systemsof the body, such as the intracranial, urinary, biliary, bronchial, andcoronary systems, thereby facilitating effective disruption and removalof occlusive material while minimizing the risk of injury to the lumenwall.

BRIEF SUMMARY OF THE INVENTION

The subject invention concerns a device and methods for disruptingand/or removing occlusive material from lumens, such as biologicallumens within the body. Although the subject invention is particularlyuseful for the disruption and/or removal of thrombus from thevasculature, it is also applicable in other lumens of the body, such asthe ureter, urethra, fallopian tubes, bile duct, intestines, and thelike. The subject invention provides for effective disruption and/orremoval of the occlusive material from the body lumen with minimal riskof injury to the lumen wall. Advantageously, the invention can be usedto achieve a high degree of removal while minimizing the amount ofocclusive material that is released into the body lumen. This isparticularly desirable in treatment of the vasculature, where therelease of emboli can be a serious risk to the patient. As described indetail below, the present invention employs a cutting means fordisrupting the thrombus, clot, embolic agent, or other occlusivematerial.

The present invention relates to an elastic sheath used for constructingocclusion disruption and/or removal devices of the invention (alsoreferred to herein as a “thrombectomy device” or “thrombolysis device”).The present invention further relates to a device for occlusion removaland/or disruption comprising a rod, an elastic sheath that ensheaths asegment of the rod, wherein the sheath has a plurality of slits, andmeans for expanding the elastic sheath, wherein the elastic sheath isdisplaced from the segment of the rod when the expansion means isactivated, and wherein the rod, the expansion means, and the elasticsheath cooperate structurally and/or functionally to form a compartmentwhen the expansion means is activated. Preferably, the expansion meansis an expandable balloon and the elastic sheath covers at least aportion of the expandable balloon and at least a segment of the rodadjacent to the expandable balloon.

The elastic sheath has a plurality of slits, with each slit separatedfrom the adjacent slit by a band of elastic material. When the expansionmeans is activated, the slits expand and a compartment (alsointerchangeably referred to herein as the “cage”) is formed through thecooperation of the rod, the elastic sheath, and the expansion means,together. When the expansion means is an expandable balloon, the ballooncan be expanded by applying pressure from within the balloon, such asair or saline pressure, for example. The device can be at leastpartially composed of an imageable material such that the position ofthe device within biological tissue, such as a biological lumen, can bereadily determined using the appropriate sensing equipment. Therefore,it is possible to accurately guide the device to a particular lumenwithin biological tissue, and to guide the device to an occluded areawithin the lumen for subsequent disruption and/or removal of theocclusive material.

In another aspect, the subject invention pertains to a method fordisrupting and/or removing occlusive material from a biological lumen byinserting the device of the invention into the lumen, placing the deviceat a point adjacent to the occlusion, activating the expansion means,and operating the device in a back-and-forth motion such that theocclusion is mechanically disrupted by abrasive contact with the bandsof the elastic sheath, and occlusive debris passes through the expandedslits, and is thereby captured within the cage of the elastic sheath.Optionally, the expansion means can be deactivated in order to narrow orclose the slits (collapsing the cage), to more securely contain theocclusive debris between the bands of the elastic sheath and the rod. Inembodiments where the expansion means is an expandable balloon, theballoon can be partially or entirely deflated in order to narrow orclose the slits and collapse the cage around the rod.

In another aspect, the present invention concerns an in vitro model ofluminal occlusion and methods for using the in vitro model to test theefficacy of devices and methods for treating luminal occlusions.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication, withcolor drawing(s), will be provided by the Office upon request andpayment of the necessary fee.

FIG. 1A shows a side view of an elastic sheath constructed in accordancewith the present invention, with the placement site of the balloonwithin the distal end of the elastic sheath. When this embodiment of theelastic sheath is utilized, one conical cage structure can be formedwhen the underlying balloon is activated at the balloon site shown.

FIG. 1B shows a side view of an elastic sheath constructed in accordancewith the present invention, with the placement site of the balloonwithin the central portion of the elastic tube. When this embodiment ofthe elastic sheath is utilized, two conical cage structures can beformed when the underlying balloon is expanded at the balloon siteshown.

FIGS. 2A-2C show side views of a rod constructed in accordance with thepresent invention, with a balloon disposed along the length of the rodand constraining material wrapped around opposing segments of theballoon and adjacent segments of the rod, leaving a segment of theballoon unwrapped and, hence, capable of expansion. In FIG. 2A, theunconstrained portion of the balloon is disposed toward the distal endof the rod. In FIG. 2B, the unconstrained segment of the balloon isdisposed toward the central portion of the rod. In FIG. 2C, twounconstrained segments of the balloon are disposed toward the centralportion of the rod, adjacent to one another.

FIGS. 3A-3C show side views of the rods shown in FIGS. 2A-2C,respectively, with the balloon expanded.

FIGS. 4A-4C show side views of devices of the subject invention in anexpanded configuration. FIG. 4A shows a device with one balloon, in anexpanded configuration, disposed toward the distal end of the rod. FIG.4B shows a device with one balloon, in an expanded configuration,disposed toward the central portion of the rod. FIG. 4C shows twoballoons, in expanded configurations, disposed toward the centralportion of the rod.

FIG. 5 shows a side view of one embodiment of the device of theinvention, in an expanded configuration, with lateral bandscross-linking the longitudinal bands, to produce a mesh.

FIG. 6 shows a plot (calibration curve) of balloon diameter versussaline pressure. A control experiment with a bare balloon was performedand compared with the device. As expected, higher pressure was requiredto inflate the modified balloon in the device.

FIGS. 7A and 7B show an in vitro human middle carotid artery (MCA) modelof the present invention, with A, B, C, D, and E representing differentlocations of the MCA. FIG. 7A shows a polypropylene tube of 2.5 mm innerdiameter (ID). FIG. 7B shows a clot holder that is a detachable siliconepouch with two openings. The clot holder is attached to thepolypropylene tube through plastic fittings.

FIG. 8 shows angiography of a right kidney and renal artery of a rabbit.

FIG. 9 shows angiography of the kidney shown in FIG. 8, with successfulthromboembolism evident.

FIG. 10 shows photographs of sliced 5 mm sections of kidney.

FIG. 11 shows a side view photograph of a device constructed inaccordance with the present invention.

FIG. 12 shows a side view photograph of another embodiment of the deviceconstructed in accordance with the present invention, with lateral bandscross-linking the longitudinal bands.

DETAILED DISCLOSURE OF THE INVENTION

The subject invention concerns a device and methods for disruptingand/or removing occlusive material from lumens, such as a blood vessel,ureter, urethra, fallopian tube, bile duct, intestine, and the like. Inaddition to biological conduits, the device and methods of the presentinvention can be utilized to disrupt and/or remove occlusive materialsfrom artificial conduits, such as those constructed for insertion intothe body (e.g., arterial or venous catheters). Where reference is madeherein to the “thrombectomy device” of the subject invention, it shouldbe understood that the device can be used to disrupt and/or removeocclusive material from any lumen, biological or artificial.

The thrombectomy device 10 of the present invention has a rod 24, anelastic sheath 40 that ensheaths at least one segment of the rod 24, andmeans for radially expanding the elastic sheath 40 around the segment ofthe rod 24. Preferably, the expansion means is at least one expandableballoon 30. In this embodiment, the thrombectomy device 10 of thepresent invention comprises the rod 24, at least one expandable balloon30 disposed along the length of the rod 24, the elastic sheath 40 thatcovers at least a portion of the expandable balloon 30 and ensheaths atleast one segment of the rod 24 adjacent to the balloon 30. Preferably,the rod 24, balloon 30, and elastic sheath 40, are co-axial.

Preferably, the means for expanding the elastic sheath 40 radially aboutthe rod 24 is an expandable balloon 30. However, other means forapplying sustained radial pressure to the inner surface of the elasticsheath 40, thereby expanding the elastic sheath 40 radially about therod 24, can be utilized. For example, expansion means can includeradially outwardly biased struts. In a deactivated state, the biasedstruts can be retained within or outside the rod 24. Upon activation,the struts are moved radially outwardly against the inner surface of theelastic sheath 40, thereby expanding the elastic sheath 40 and deployingthe cage 50 (see, for example, U.S. Pat. No. 5,911,734, Tsugita et al.,which describes a filter and strut structure). In a further embodiment,a compressive spring may be employed which pulls fore and aft ends ofexpandable struts together, thereby expanding the elastic sheath 40. Inother words, the elastic sheath 40 is spring activated. Alternatively,the elastic sheath 40 can be expanded by a radially expandable framestructure comprising frame struts (see, for example, U.S. Pat. No.6,277,139, Levinson et al., which describes a frame structure attachedto perforated filter material).

The elastic sheath 40 has a plurality of slits 20, with each slit 20separated from the adjacent slit 20 by a band 21 (or string) of elasticmaterial. The slits 20 can be on one side of the expansion means,proximal or distal to the expansion means, or on both sides of theexpansion means, proximal and distal to the expansion means. When theexpansion means is activated to radially expand the elastic sheath 40about the rod 24, a portion of the elastic sheath 40 will be displacedfrom a segment of the rod 24 that it previously ensheathed, the slits 20expand, forming a compartment 50 (also interchangeably referred toherein as the cage 50 or cage structure 50) around the rod 24. Thus, inembodiments where an expandable balloon 30 is the expansion means, whenthe balloon 30 is radially expanded about the rod 24 via internalpressure, such as air pressure or saline pressure, portions of theelastic sheath 40 that are adjacent to the balloon 30 are displaced fromthe rod 24, and the slits 20 expand, forming a roughly cone-shapedcompartment 50 around the rod 24.

As used herein to describe the cage 50 of the subject invention, theterms “cone-shaped”, “conical”, and “frustoconical” are intended toinclude shapes that linearly, parabolically, or hyperbolically taperfrom the expansion means (such as the balloon 30) down the length of therod 24. Any expansion means that radially expands the elastic sheath 40to cooperate with the rod 24 in forming the cage 50 is sufficient. Theconical body of the cage 50 extends (at its broadest point) expansionmeans to a proximal or distal point (its narrowest point) on the rod 24,as shown in FIGS. 4A-4C and FIG. 5. Therefore, one end of the cage 50 isenlarged in diameter when the expansion means is activated and theelastic sheath 40 is displaced radially (outwardly from the rod 24), andthe other end of the cage 50 tapers to the rod 24, away from theexpansion means. In this way, in those embodiments wherein the expansionmeans is one or more expandable balloons 30, the cage 50 of thethrombectomy device 10 is “balloon-activated”.

When the expansion means is not activated, the elastic sheath 40 (and,hence, the longitudinal bands 21) is in a position of repose (collapsed)in which it is preferably substantially flush with the rod 24. Theconical cage 50 can be a unilateral cage, forming on one side of theexpansion means, or a bilateral cage, forming on both sides of theexpansion means. If the expansion means is a continuously solidstructure, such as an expandable balloon 30, the bilateral cages will beseparated by the expansion means. However, the expansion means can be adiscontinuously solid structure, having voids through which the cageswould be in communication.

The rod 24 of the device 10 is preferably highly flexible to facilitatenavigation through tortuous biological lumens. The rod 24 can be hollowor solid, and can be composed of one or more of a variety of materials,such as melt-processable and/or non-melt-processable fluoropolymers(e.g., perfluoroalkoxy (PFA); fluorinated ethylene propylene (FEP);poly(tetrafluoroethylene) (PTFE); tetrafluoroethylene (MFA); ethylenetetrafluoroethylene (ETFE); poly(vinylidene fluoride) (PVDF); ethylenechlorotrifluoroethylene (ECTFE); andpoly(tetrafluoroethylene-co-perpropylvinylether) (PTFE/PPVE));polyurethane; polyethylene; nylon; PEBAX, polyvinylchloride (PVC);thermoplastic elastomers; polyesters; and radio-opaque andnon-radio-opaque resin blends. If the rod 24 is composed of one or morepolymers, the rod 24 can optionally include one or more fillers, such asbarium sulfate (BaSO₄), bismuth trioxide (Bi₂O₃), bismuth subearbonate(Bi₂CO₃), and tungsten (W). Optionally, the rod 24 can include braidedwire for enhanced torque capabilities, as long as the rod issufficiently flexible and kink-resistant for the particular application.Braid wire density, which is described as picks per inch (PPI), i.e.,the number of wire crossovers per inch of rod, can be optimized by thoseskilled in the art. The rod 24 can have any of a variety of shapes incross-section. Preferably, the rod 24 has a substantially circularcross-section. The length and diameter of the rod 24 will depend on thediameter of the lumen and the target site. For example, the length ofthe rod 24 can be within the range of about 50 centimeters to about 300centimeters for many applications, and from about 2.5 F (french) toabout 10 F in diameter. Preferably, the length of the rod 24 is about150 centimeters and the diameter of the rod 24 is about 0.25millimeters.

The elastic sheath 40 has the general shape of a tube, with a first end12 with an opening 16 and a second end 14 with an opening 18. When thedevice 10 is assembled, the rod 24 runs through the openings 16, 18 ofthe elastic sheath 40.

Preferably, the elastic sheath 40 is produced from an extremelyflexible, tear-resistant, biocompatible polymer tube, which can becomposed of any of a variety of commercially available thermoplasticelastomers. For example, in order to produce the elastic sheath 40,slits 20 can be made in polymer tubes composed of any of a variety ofmaterials, such as silicone, polyurethane, silicone-polyurethanecopolymer, styrene-ethylene-butylene-styrene (copolymer), and othersuitable elastomeric materials. The elastic sheath 40 should besufficiently flexible and resilient such that when a radial force isapplied outward from within the sheath 40 (e.g., by the expandingballoon 30), the elastic sheath 40 will expand at the point the force isapplied, but will have sufficient memory to revert to its regulartubular shape when the force is removed.

The elastic sheath 40 has a plurality of slits 20. The slits 20 can beuniformly spaced from one another or non-uniformly spaced from oneanother. Preferably, the slits 20 are longitudinally arranged around atleast a portion of the circumference of the elastic sheath 40, or aroundentire circumference of the elastic sheath 40. However, the slits 20 canbe arranged non-longitudinally on the elastic sheath 40. For example,the slits 20 can be arranged at a diagonal relative to the length of thesheath 40. The slits 20 are preferably substantially parallel to oneanother. In one embodiment, the slits 20 are arranged transverse to thelength of the sheath 40. In another embodiment, the slits 20 arearranged non-transverse to the length of the sheath 40.

In one embodiment, the elastic sheath 40 has within the range of 2 to 12slits 20 proximal to the expansion means. In another embodiment, theelastic sheath 40 has within the range of 2 to 12 slits 20 distal to theexpansion means. In another embodiment, the elastic sheath 40 has withinthe range of 2 to 12 slits 20 both proximal and distal to the expansionmeans.

The elastic sheath 40 preferably has a length within the range of about5 millimeters and about 5 centimeters, and a diameter within the rangeof about 1 millimeter and about 1 centimeter. Preferably, the elasticsheath 40 has a thickness within the range of about 0.05 millimeters andabout 2 millimeters.

FIG. 1A shows a side view of an elastic sheath 40 constructed inaccordance with the present invention, with the placement site 22 of theballoon 30 within the distal end of the elastic sheath 40. When thisembodiment of the elastic sheath 40 is utilized, one conical cagestructure 50 can be formed when the underlying balloon 30 is activatedat the balloon site 22 shown. In FIG. 1A, the longitudinal slits 20extend from an area of the elastic sheath 40 in close proximity to theballoon 30 and the first end 12 of the elastic sheath 40, to the secondend 14 of the elastic sheath 40, permitting formation of the conicalcage 50 that extends from the balloon 30 to the point where thelongitudinal slits 20 terminate. FIG. 1B shows a side view of an elasticsheath 40 with the placement site 22 of the balloon 30 within thecentral portion of the elastic sheath 40. When this embodiment of theelastic sheath 40 is utilized, two conical cage structures 50 can beformed (proximal and distal to the balloon 30) when the underlyingballoon 30 is expanded at the balloon site 22 shown.

FIGS. 2A-2C show side views of a rod 24 constructed in accordance withthe present invention, with a balloon 30 disposed along the length ofthe rod 24 and constraining material 28 wrapped around opposing sides ofthe balloon 30 and adjacent segments of the rod 24, leaving theunconstrained segment of the balloon 30 capable of expansion. In FIG.2A, the unconstrained segment of the balloon 30 is disposed toward thedistal end 26 of the rod 24 and toward the distal end of the elasticsheath 40. In FIG. 2B, the unconstrained segment of the balloon 30 isdisposed more toward the central portion of the rod 24 (as compared toFIG. 2A) and approximately in the center of the elastic sheath 40. InFIG. 2C, two unconstrained segments of the balloon 30 are disposedtoward the central portion of the rod 24, adjacent to one another, andapproximately in the center of the elastic sheath 40. In an alternativeembodiment, instead of leaving two or more segments of a single balloonunconstrained, two or more separate balloons 30 can be utilized.

FIGS. 3A-3C show side views of the rods shown in FIGS. 2A-2C,respectively, with the balloons 30 expanded. FIGS. 4A-4C show threeembodiments of the device 10 in an expanded configuration (i.e., withthe cage 50 deployed). As shown in FIG. 4A, the elastic sheath 40 can beplaced on the rod 24 such that the expandable balloon 30 is off centerrelative to the length of the elastic sheath 40. In this way, the sizeof the expanded cage 50 can be varied. Further, as shown in FIG. 4B, theelastic sheath 40 can be placed on the rod 24 such that the expandableballoon 30 is approximately in the center of the elastic sheath 40,which provides two cages 50 when then the device 10 is in an expandedconfiguration (the balloon 30 is expanded). FIG. 4C demonstrates thatthe device 10 may comprise a balloon 30 with two or more unconstrainedsegments (also shown in FIG. 2C, unexpanded and without the elasticsheath 40; and in FIG. 3C, expanded and without the elastic sheath 40).Alternatively, instead of leaving two or more segments of a singleballoon unconstrained, two or more individual balloons 30 can beutilized.

FIG. 5 shows a side view of one embodiment of the device 10 of theinvention, in an expanded configuration, with lateral bands 34cross-linking the longitudinal bands 21 such that the expanded cage 50resembles a mesh. The lateral bands 34 can bridge longitudinal bands 21at any of a variety of acute, obtuse, or right angles relative to thelongitudinal bands 21 which they interconnect. When the device 10 isoperated, the lateral bands 34 function to shear the occlusive materialand enhance the ability of the cage 50 to retain disrupted occlusivedebris. The lateral bands 34 can be formed integrally within the elasticsleeve 40, in a similar fashion as the longitudinal bands 21.Alternatively, the lateral bands 34 can be subsequently added andsecured to the longitudinal bands 21.

Preferably, the expandable balloon 30 is spherical or substantiallyspherical such that, when the balloon 30 is expanded, a “cage” isformed. However, the balloon 30 can be any shape which, when expanded,also stretches and expands the longitudinal slits 20 and longitudinalbands 21, permitting sufficient disruption of occlusive material and,preferably, capture by the cage 50. For example, the expandable balloon30 can be ring-shaped, permitting blood flow through the hole of thering. Preferably, the balloon 30 is disposed concentrically around aportion of the rod 24, as shown in FIGS. 11 and 12, or at its distal end26. When the device 10 is in an expanded configuration, the balloon 30,cage 50, and the rod 24 define a holding compartment to collect and holdocclusive debris material. The balloon 30 can be arranged on the rod 24in any of a variety of ways permitting expansion of the balloon 30 andformation of the cage 50 defining the holding compartment, includingmany balloon-catheter arrangements known in the art (e.g., FOGARTYembolectomy catheter; SENTRY balloon catheter; EQUINOX occlusion balloonsystem; U.S. Pat. Nos. 3,435,826; 5,824,037; 4,762,130; 5,250,029;4,403,612; 3,467,101; 5,232,445; 4,919,651; 4,637,396). The balloon 30can be mounted longitudinally or transversally on the rod 24, forexample. Appropriate means for expanding the balloon 30, such as byapplying internal pressure to the balloon 30, can likewise be employed.For example, the rod 24 can include one or more openings along itslength that are in fluid communication with the interior of the balloon30, permitting passage of fluid (e.g., gas or liquid) between theinterior of the hollow rod 24 and the interior of the balloon 30, asdescribed in U.S. Pat. No. 3,435,826. The rod 24 of the device 10 caninclude concentric or non-concentric interior lumens or an external tubeconnecting the balloon 30 to an external source of pressurized fluid.The expandable balloon 30 can be composed of any of a variety ofmaterials. Preferably, the balloon 30 is a biocompatible elasticmaterial, such as synthetic or natural rubber latex, silicone,polyurethane, polyisoprene styrene-ethylene-butylene-styrene blockcopolymer (SEBS), or other suitable elastomeric material.

At least a portion of the balloon 30 can be radially constrained,leaving at least one portion of the balloon 30 radially unconstrained.In this way, when pressure is applied to the constrained balloon 30, theunconstrained portion or unconstrained portions of the balloon 30 expandbut the constrained portion or portions do not. In one embodiment, anelongated, tube-shaped balloon 30 is utilized (such as an angioplastyballoon), wherein the balloon 30 is radially constrained at either orboth ends, leaving one or more segments of the balloon 30 unconstrained.In this way, when pressure is applied to the constrained balloon 30, theunconstrained segment or unconstrained segments of the balloon 30preferably expand to form a sphere or substantially spheroid shape. Theradial constraint can be provided in any of a number of ways. Forexample, radial constraint can be provided by a constraining material 28that surrounds and radially constrains portions of the balloon 30 (e.g.,segments of the balloon 30 at either or both ends). The constrainingmaterial 28 prevents those portions of the balloon 30 that theconstraining material 28 surrounds from expanding, leaving the rest ofthe balloon 30 (e.g., the center portion of the balloon 30) capable offull expansion. For example, the constraining material 28 can be afiber, such as polyurethane fiber (e.g., SPANDEX), that is wrappedaround those portions of the balloon 30 to be constrained.

When the balloon 30 is expanded, the balloon 30 preferably has adiameter within the range of about 1 millimeter to about 3 centimeters,and a length within the range of about 1 millimeter to about 1centimeter. Preferably, the thickness of the balloon 30 is within therange of about 0.01 millimeter and about 0.5 millimeter.

The thrombectomy device 10 of the present invention is particularlyuseful for treating vascular thrombosis and pathological conditionsassociated with vascular thrombosis, such as ischemic thromboembolicstroke. Because the device 10 of the subject invention can beconstructed so as to be highly flexible and maneuverable, the device 10will be suitable for operation in previously inaccessible anatomicalregions, such as intracranial, urinary, biliary, bronchial, coronary, orother physiological lumen systems. Due to its elastic property, the cage50 can be expanded and contracted multiple times to obtain optimal sizeand position before it is used to retrieve occlusive debris. Because ofthe soft, elastic property of the longitudinal bands 21 of the sheath40, the device 10 will cause minimal trauma to the endothelial cellularlayer. Advantageously, the size of the cage can be controlled. The cageis formed only when the balloon is deployed by pressure. The higher thepressure applied to the balloon, the larger the cage's size. Inaddition, it will be possible to work with a variety of lumen sizes withthe same device.

In another aspect, the subject invention pertains to a method fordisrupting and/or removing occlusive material from a biological lumen,such as a blood vessel. The for sake of simplicity, the method will bedescribed wherein the expansion means is an expandable balloon 30.However, other means for expanding the elastic sheath 40 to form thecage 50 can be utilized. The method is carried out by inserting thedevice 10 of the invention into the lumen, placing the expandableballoon 30 and cage 50 at a target site within or adjacent to theocclusion, expanding the balloon 30, and operating the device in aback-and-forth and, optionally, twisting motion such that the occlusionis mechanically disrupted by shearing contact with the longitudinalbands 21 of the elastic sheath 40, or with the longitudinal bands 21 andlateral bands 34, depending upon the particular embodiment.Advantageously, occlusive fragments and debris material produced byexpansion of the balloon 30 against the occlusion and/or shearingcontact of the occlusion with the bands 21, pass through the expandedslits 20, and are thereby captured within the cage formed by theexpanded elastic sheath 40. Advantageously, although the longitudinalbands 21 of the device 10 may contact the luminal wall, little or nodamage to the luminal wall results. Optionally, the balloon 30 can thenbe partially or entirely deflated, in order to narrow or close the slits20, thereby more securely containing the disrupted occlusive debrismaterial between the bands 21 of the elastic sheath 40, the balloon 30,and the rod 24. The device 10 is then removed from the patient.

For example, an incision can be made and the device 10 of the subjectinvention can be inserted through an artery, such as the femoral arteryin the patient's groin, and directed to the site of the occlusion. Thedevice 10 can be inserted and positioned at a point in the lumen before,within, or beyond the occlusion. Either end of the device 10 can beinserted first into the lumen, so long as the longitudinal bands 21and/or lateral bands 34 can make searing contact with the occlusion,thereby disrupting the occlusion and, optionally, providing anopportunity for the expanded cage 50 to capture particles from thedisrupted occlusion.

Once the device 10 is in place, the means for expanding the balloon 30can be activated. For example, the device 10 can be in operablecommunication with a pump that provides gas or fluid (e.g., salinesolution) to the balloon 30. The balloon 30 can be expanded to such anextent that the balloon 30 makes radial contact with the inner walls ofthe lumen or occlusive material deposited on the luminal walls.Optionally, the balloon 30 can be expanded to such an extent that thelumen becomes dilated, as during angioplasty procedures. Physicians ofordinary skill in the art can determine optimal pressures to be appliedto the balloon 30, optimal diameters to which the balloon 30 is to beexpanded within the occluded lumen, and durations of balloon 30expansion. The operator of the device 10 can use a back-and-forth and/ortwisting motion in order to facilitate disruption and capture of theocclusive material within the cage 50. The balloon 30 can then bedeflated, contracting the cage 50, and the device 10 can be withdrawnfrom the biological lumen. Preferably, the device 10 is operated suchthat any occlusive debris freed by the device is maintained proximallyof the balloon 30 and the distal rod end 26, thereby minimizing the riskof occlusive debris migrating to a remote site.

Optionally, the thrombolytic device 10 of the subject invention can beused in conjunction with various pharmacologic substances that breakupor dissolve the occlusion, and/or prevent the formation of futureocclusions. For example, in the case of blood clots (also known asthrombi), various anticoagulant, thrombolytic (so called “clot-busting”drugs) or anti-platelet agents can be administered orally orintravenously. Examples include heparin (CALCIPARINE, HEPATHROM,LIP-HEPIN, LIQUAEMIN, PANHEPRIN), warfarin (ATHROBMIN-K, PANWARFIN),tissue plasminogen activator (tPA; ALTEPLASE; ACTIVASE), streptokinase(KABIKINASE, STREPTASE), urokinase (ABBOKINASE), anistreplace,aminocaproic acid, aprotinin, acetylsalicylic acid (aspirin),dipyridamole (PERSANTINE), abciximab (CENTOCOR), dalteparin (FRAGMIN),enoxaparin (LOVENOX), hirudin (DESIRUDIN), 4-hydroxycoumarin (COUMADIN),lepirudin (REFLUDAN), protamine sulfate, phytonadione (Vitamin K₁),reteplase (RETAVASE), and ticlopidine (TICLID). Many of these agentsoperate by inhibiting the clotting mechanism (anticoagulants), lysingthrombi (fibrinolytic agents), and interfering with platelet adhesionand/or aggregation.

Various components of the thrombolytic device 10, such as the rod 24,the elastic sheath 40, and/or the expansion means (such as theexpandable balloon 30), can be impregnated or coated with one or morebiologically active agents, such as pharmacologic substances thatbreakup or dissolve the particular occlusion to be removed. Thebiologically active agents can function on contact with the device 10 orthe substances can be released from the device 10 into the biologicallumen in a controlled release fashion. Optionally, the biologicallyactive agents can be released and/or become activated upon contact withblood, or otherwise be responsive to the physiological environment. Forexample, the biologically active agents can be temperature-sensitiveand/or pH-sensitive. As an alternative to impregnated or coatedcomponents, the biologically active agent can be delivered by othermeans, such as a port on the rod 24 of the device 10 that permitsinjection of the biologically active agent at a target site. As usedherein, the term “biologically active agent” refers to any substancethat is capable of promoting or causing a therapeutic effect in apatient.

Methods known in the art for insertion and operation of an angioplastycatheter can also be utilized with the device 10 of the presentinvention. For example, the device 10 of the present invention can beintroduced into a biological lumen through an introducer (also known asan introducing catheter), which is used to access the lumen. Guide wirescan also be utilized.

As indicated above, where reference is made herein to the “thrombectomydevice” or “thrombolytic device” of the subject invention, it should beunderstood that these terms are used herein interchangeably and thedevice can be used to disrupt and/or remove any occlusive material fromany lumen, whether the occlusive material and lumen are biological orartificial. For example, in addition to disrupting and, optionally,removing thrombus or other endogenous embolic material, such ascalcifications, cholesterol, plaque, etc., from a biological lumen, thedevice 10 of the present invention can be used to disrupt and/or removeexogenous embolic material, such as embolic agents. Embolic agents thatcan be disrupted and/or removed with the device 10 of the presentinvention include, but are not limited to, adhesive (such aspolymerizing adhesive), gel, silicone rubbers, urethanes and otherorganic elastomers, polymerizable protein solutions, silk sutures,polyvinyl alcohol (PVA) particles, cross-linked polyvinyl alcohol foam,polyurethane foam, acrylic polymers, polyethylene foam, silicone foam,fluorinated polyolefin foam, and/or an ethylene-vinyl-alcohol copolymercommercially available under the designation ONYX by MICRO THERAPEUTICS,INC (Irving, Calif.) (Dehdashti, A. R. et al., Neurosurg. Focus11(5):1-6, 2001; Halbach V. V. et al., AJR 153:467-476, 1989; Purdy P.D. et al., J. Neurosurg. 77:217-222, 1992; Purdy P. D. et al., Am. J.Neuroradiol. 11:501-510, 1990).

ONYX is a liquid embolic (or embolization) agent that is a mixture ofethylene-vinyl alcohol copolymer (EVOH), dimethyl sulfoxide (DMSO), andmicronized tantalum (to enable visualization under fluoroscopy) that canbe used to fill aneurysms. Contact of ONYX with blood results in itssolidification from the outside inward, thereby forming a spongypolymeric cast (Jahan R. et al., Neurosurgery 48(5):984-997, 2001;Hamada J. et al., J. Neurosurg. 97(4):889-895, 2002; Hamada J. et al.,Am. J. Neuroradiol. 17(10):1895-1899, 1996). The ONYX embolic agent canbe used for the treatment of aneurysms and arterio-venous malformations(AVMs), two conditions which can lead to hemorrhagic stroke. Oncedelivered inside the targeted malformation, the ONYX embolic agentquickly solidifies into a spongy polymer mass designed to seal off thedefective portion of the vessel. In aneurysm and AVM applications, theONYX filling is intended to reduce the risk of rupture and subsequentstroke. The device 10 of the present invention can be used to disruptand/or remove excess or otherwise undesired ONYX material present withina vessel.

Depending upon the occlusive material to be removed or retrieved,disruption or breaking apart of the occlusive material may not benecessary. For example, where the device 10 of the present invention isused to retrieve embolization devices, such as those used in the fieldof cardiology for treating aneurysms, no disruption of the embolizationdevice may be necessary and the embolization device may simply becaptured with the cage 50 of the device 10 of the present invention andpulled out of the biological lumen. Examples of such embolizationdevices include, but are not limited to, PVA particles, detachableballoons, and embolization coils. Advantageously, large or small amountsof occlusive material can be removed using the device 10 of the presentinvention. The occlusive material can be any occlusive or potentiallyocclusive material that can be dislodged from the luminal wall and/orcaptured by the cage 50 of the device 10. The occlusive material can beof various phases, such as solid, semi-solid, or liquid.

Optionally, any component of the thrombectomy device 10 of the subjectinvention can be at least partially composed of an imageable material.For example, the rod 24, balloon 30, and/or elastic sheath 40, can becomposed of an imageable material. As used herein, an “imageablematerial” includes those materials the location of which can bediscerned within a given opaque, ambient medium such as biologicaltissue, using the appropriate sensing equipment, such as imagingequipment. The imageable material selected should have an image“signature” discernibly different from that of the surrounding mediuminto which the device 10 is to be introduced. Components of the device10 can be coated or impregnated with one or more imageable materials,for example.

In one embodiment, the imageable material is an echogenic material withan acoustic impedance different from that of the surrounding medium(i.e., high acoustic impedance differential), enabling the thrombectomydevice 10 to be imaged using a sonic imaging device (e.g., ultrasoundimaging equipment). A variety of materials that are echogenic (i.e.,sound reflective) can be utilized, such as aluminum, hard plastic, sand,and metal particles. For example, the echogenic material can be any ofthose materials described in U.S. Pat. No. 5,201,314 and U.S. Pat. No.6,106,473, or a combination of those materials. In another embodiment,the imageable material is a radio-opaque material (such as bariumsulfate, tantalum, and/or gadolinium particles) that can be imaged withradiographic equipment (e.g., an x-ray machine or computed tomography(CT) scanner). In a further embodiment, the imageable material is asubstance that can be imaged using magnetic resonanceimaging/spectroscopy (MRI/MRS) equipment. Other imageable materialsinclude those materials detectable through single photon emissiontomography (SPECT) or positron emission tomography (PET), for example.The component or components of the thrombectomy device 10 can be whollyor partly composed of the imageable material. As indicated above, theimageable material can be in the form of a coating or film on anunderlying substrate.

Contrast media, such as dyes, can also be used in conjunction with theappropriate imaging equipment in order to discern more details withinthe biological lumen. For example, barium-containing andiodine-containing dyes can be administered in conjunction with x-ray orCT imaging. Gadolinium, for example, can be used in conjunction with MRIimaging.

Optionally, the device 10 of the present invention can further include ameans for providing a jet or jets of fluid under pressure to the distalend 26 of the rod 24, and/or at any point or points along the rod'slength. For example, the rod 24 of the device 10 can be hollow and inoperable communication with a pump that provides fluid under pressure tothe distal end of the rod 24, where it exits the rod 24 through anoutlet. The fluid jet can facilitate disruption of occlusions within thebiological lumen.

Optionally, the device 10 of the present invention can include a meansfor vacuuming occluding debris from the lumen at the distal end 26 ofthe rod 24, and/or at any point or points along the rod's length. Forexample, the rod 24 of the device 10 can be hollow and in operablecommunication with a means for providing negative pressure to theinterior of the rod, such that occlusive debris is drawn into inletsalong the length and/or the end of the rod 24. Optionally, the device 10can include both a jet means and a vacuum means, as described above. Inone embodiment, the jet means and vacuum means can be alternativelyoperated to expel fluid from the device 10, in order to disrupt anocclusion, and to take up the occlusive debris upon activation of thevacuum means.

In addition to natural biological conduits of the body, such as bloodvessels (veins, arteries, etc.), ureter, urethra, fallopian tube, bileduct, intestine, and the like, the device 10 and methods of the presentinvention can be utilized to remove occlusive materials from otherbiological or artificial conduits, such as arterial or venous catheters,stents, grafts, such as peripheral femoral-popliteal, coronary bypassgrafts and dialysis access grafts, and fistulas.

The occlusion-removing device 10 of the present invention can beutilized to disrupt and/or remove occlusive material from natural orartificial lumens within humans or animals, such as non-human mammals.Thus, the device 10 of the present invention can be used in a variety ofveterinary applications in order to treat domesticated ornon-domesticated animals. The dimensions of the various components ofthe device 10 can be optimized for the particular animal subject.

In another aspect, the present invention concerns a device 60 useful asan in vitro model of luminal occlusion, such as that shown in FIGS. 7Aand 7B, and methods for using the device 60 to test the efficacy ofdevices and methods for treating luminal occlusions. The device 60includes a flexible hollow tube 61 having a first end 62 and second end64. The flexible tube 61 can be composed of any material, such assilicone, which permits bending of the tube 61 into a tortuous shape, ifdesired. For example, the flexible tube can be composed of one or moremelt-processable or non-melt-processable polymers; polyurethane;polyethylene; nylon; PEBAX, polyvinylchloride (PVC); thermoplasticelastomers; polyesters; and resin blends.

As shown in FIG. 7A, one or more bends can be placed in the tube 61 inorder to simulate vasculature of the brain, for example. At one or morepoints along the length of the tube 61, occlusion sites can beestablished. In one embodiment, each occlusion site (A, B, C, D, E) hasa three-way receptacle 66 (also referred to herein as a “clot holder”)with ports 68 (also referred to herein as “fittings”) connecting thereceptacle 66 to the tube 61. The three-way receptacle 66 contains anocclusion 70, such as a naturally occurring or artificial clot. Thereceptacle 66 can her include an access port 73 for inserting anocclusion 70. The diameter and length of the tube 61 are preferably ofdimensions to accommodate a particular test device to be inserted intothe first or second ends 62, 64 of the tube 61 and to mimic theparticular artificial or biological lumen to be modeled. Optionally, thetube 61 can have one or more branches and sub-branches. The tube 61 cancontain a fluid, such as saline or blood, to mimic a biological vessel.The test device can be inserted into either end of the tube 61 andnavigated to an occlusion site to act on an occlusion 70. Theperformance of the test device can then be evaluated. Test criteria willdepend upon the nature of the technique and/or test device and theobjective to be achieved.

The terms “comprising”, “consisting of” and “consisting essentially of”are defined according to their standard meaning. The terms may besubstituted for one another throughout the instant application in orderto attach the specific meaning associated with each term.

As used in this specification and the appended claims, the singularforms “a”, “an”, and “the” include plural reference unless the contextclearly dictates otherwise. Thus, for example, a reference to “anexpandable balloon” includes more than one such balloon. A reference to“an elastic sheath” includes more than one such sheath. A reference to“a compartment” (i.e., “a cage”) includes more than one suchcompartment. A reference to “an occlusion site” includes more than onesuch occlusion site, and the like.

All patents, patent applications, provisional applications, andpublications referred to or cited herein, whether supra or infra, areincorporated herein by reference in their entirety to the extent theyare not inconsistent with the explicit teachings of this specification.

Following are examples which illustrate procedures, including the bestmode, for practicing the subject invention. These examples should not beconstrued as limiting. All percentages are by weight and all solventmixture proportions are by volume unless otherwise noted.

Example 1 Construction of a Thrombectomy Device

A thrombectomy device of the subject invention has been made in amodular fashion. The device consists of an elastomeric polymer tube ofan appropriate size and a balloon catheter.

Tubes were made from CARBOSIL 40 90A (The Polymer Technology Group,Inc., Berkeley, Calif.), a solution grade elastomeric, tear-resistantsilicone-polyurethane thermoplastic copolymer, by the dip-coatingmethod. Several 21 (0.80 mm outer diameter, OD) gauge injection needles(MONOJECT from Sherwood Medical, St. Louis, Mo.) were used as moldsubstrates. Each needle was 1.5 inches long and the size (OD) of theneedle represents approximately the inner diameter (ID) of the resultingtube. Two times dipping of each needle in 15 wt % polymer solution intetrahydrofuran (THF) at about a 4 mm/sec withdrawal rate and a 30minute interval between two successive dippings formed an approximately90 μm thick polymer coating. Coated needles were then vacuum-dried.Coating on both ends of the needle was non-uniform. Therefore, keeping auniform section of 30 mm long coating around the middle of the needle,the remaining coating was carefully cut by a sharp surgical razor blade(MILTEX Surgical Blades, model 4197 #11, MILTEX Instrument Company,Inc., Bethpage, N.Y.) and then removed. At this point, the coating couldbe detached in the form of a uniform tube.

Without detaching the coating from the needles, a pattern was made onthe coating manually by a sharp black permanent marker, as shown inFIGS. 1A and 1B, (SHARPIE Ultra Fine Point Permanent Marker from SANFORDCorporation, Bellwood, Ill.). The pattern was along the length andaround the needle. A total of 5 slits 20 were then cut along the patternwith a stainless steel surgical blade of about 10 μm tip size. Slits 20were 10 mm long and the spacing between two slits 20 (defining a band 21there between) was about 550 μm. This step was carried out under amicroscope. Needles were then immersed in 60% acetone in water (V/V) for5 minutes for swelling the polymer. The coating was then detached in theform of a uniform tube when pushed lightly off the needle. The actualmodified polymer tube is shown in FIG. 11.

A SENTRY balloon catheter was purchased from BOSTON SCIENTIFIC-TARGET,Fremont, Calif. The balloon diameter and the balloon length were 3.5 mmand 10 mm when inflated. The balloon portion of the catheter wasmodified by constraining more of the proximal end of the balloon thanthe distal end, as shown in FIG. 2A, or by constraining about equalportions of the proximal end and distal end of the balloon, as shown inFIGS. 2B and 2C. The modified balloon portion was 2 mm long. This wasdone by wrapping around a stretchable, segmented polyurethane fiber (ThePolymer Technology Group Inc., Berkeley, Calif.). Prior to wrapping, thefiber was pre-stretched to about 100% of its original length. Whenpressure was applied by injecting saline solution, only theunconstrained segment of the balloon 30 inflated, as shown in FIGS.3A-3C.

The modified polymer tube was then swelled by immersion in 60% acetonein water (V/V) for 5 minutes. Swelling of approximately 40% of itsoriginal size occurred. The swelled tube was then slipped over themodified balloon in a desired location. The ID of the tube was smaller(about 0.2 mm) than the OD of the balloon. Once dried under the vacuum,the elastomeric tube captured the modified balloon firmly, as shown inFIGS. 4A-4C, with the actual device shown in FIG. 11.

Two preliminary tests were performed on the thrombectomy device:mechanical testing and in vitro performance testing.

Example 2 Mechanical Testing of a Modified Balloon Under Applied SalinePressure

To determine the inflated balloon size with respect to the appliedsaline pressure, the device was installed on a micromanipulator. Using adigital inflation device and fluid dispensing syringe (MONARCH 25, MERITMEDICAL SYSTEMS, Inc., South Jordan, Utah) the saline pressure wasapplied. The micromanipulator read the inflated balloon diameter quiteaccurately at different saline pressures. The digital inflation deviceshowed the applied saline pressure directly. A plot (calibration curve)of balloon diameter versus saline pressure was constructed as shown inFIG. 6. A control experiment with a bare balloon was performed andcompared with the device. As expected, higher pressure was required toinflate the modified balloon in the device. This type of calibrationcurve will be helpful for both in vitro and in vivo device operation.

Example 3 In Vitro Performance Testing of the Thrombectomy Device inSilicone Tubing

40 cm long silicone tubing (ID 2.5 mm) was selected for the preliminaryin vitro performance testing of the device 60. Two syringes were placedat both ends of the tube 61. Due to the flexible nature of the tube 61,an approximately tortuous shape could be given without kinking, as shownin FIG. 7A. Rabbit blood clots were used as models for the experiment. 1ml of blood was allowed to coagulate in a 7 ml sterile blood collectiontube for a period of 1 hour. The tube 61 was then opened and the bulkclot was removed and cut in half. Each section was weighed and recorded.The silicone tube 61 was prepared by flushing it with saline solution toremove any air bubbles from the tube 61. The blood clot was placed in a3 ml syringe and injected into the silicone tube 61. Saline was theninjected into the silicone tube 61 until the clot reached approximately20 cm from the proximal end (first end, 62) of the tube 61. The syringeon the distal end (second end, 64) was kept attached to the siliconetube 61, but the proximal syringe was replaced with a 3-way device thatallowed the catheter to be inserted.

The thrombectomy device 10 was first navigated through the tube 61 andpassed through the emboli. The thrombectomy device 10 was then slowlydeployed up to a desired size (about 2.2 mm) and pulled back. The cagestructure was able to grab the emboli and move it out of the tube 61.

Example 4 Materials for Making the Elastic Sheath

This component is the most important part of the thrombectomy devicebecause it will directly contact and manipulate the thrombus. A modifiedballoon catheter will assist this component to make its cage-like shapewhen deployed.

Tear-resistant biocompatible elastomeric polymer materials will bechosen for making tubes. Two types of commercially available solutiongrade (SG) thermoplastic materials will be selected: a polyurethane(TECOFLEX SG-80A, THERMEDICS Polymer Products, Woburn, Mass.); and a fewsilicone-polyurethane copolymers (CARBOSIL 40 90A, PurSil 20 80A andPurSil AL5 75A, The Polymer Technology Group Inc., Berkeley, Calif.).TECOFLEX SG-80A is an aliphatic polyether-based thermoplasticpolyurethane (TPU). PURSIL silicone-polyether-urethane and CARBOSILsilicone-polycarbonate-urethane are thermoplastic copolymers containingsilicone in the soft segment. PURSIL 20 80A is an aromatic siliconepolyetherurethane whereas PURSIL AL5 75A is an aliphatic siliconepolyetherurethane. Table 1 lists some of the physical test data of thesematerials reported by the manufacturers. From the table it is clear thatthese materials cover a range of mechanical properties. The purpose ofselecting all four materials under this study is to find the rightmaterial for the optimized device.

TABLE 1 Physical Test Data of Elastomeric Polymer Materials TensileStress Tensile Stress at 100% at 300% Ultimate Ultimate ElongationElongation Tensile Elongation Tear Strength, Elastomer (psi) (psi)Strength (psi) (%) die “C” (pli) TECOFLEX 300 800 5800 660 N/A EG-80APURSIL 20 270 570 5300 900 390 80A PURSIL 900 1630 4900 770 115 AL5 75ACARBOSIL40 1310 2400 4300 530 500 90A

The data for TECOFLEX EG-80A represent data for extrusion gradematerials. The solution grade data are not available. The solutiongrades differ from the extrusion grades in that they contain no meltprocessing lubricants.

If required, in order to clearly visualize the tube under a fluoroscopewhile performing in vivo tests, the tube can be constructed so as to beradio-opaque. Radio-opaque grade TECOFLEX is available with 20 wt % and40 wt % loading of barium sulfate. Other polymers could be eitherblended with barium sulfate or could be custom-blended from themanufacturer.

The dip-coating method will be used to make polymer tubes. TECOFLEXEG-80A is soluble in N,N-dimethylacetamide (DMAC), and othersilicone-polyurethane copolymers are soluble in tetrahydrofuran (THF).Tubes will be made using 21 gauge needles (OD 0.8 mm). The innerdiameter (ID) of the tube will be 0.8 mm or little less, if the polymershrinks after drying. Tube thickness generally depends upon threeparameters: the polymer concentration; the total number of dippings; andthe withdrawal rate. By proper adjustment of these three parameters,tubes will be made of about 100 μm in thickness. Table 2 shows thedetails.

TABLE 2 Elastic Sheath Design Calculated spacing between Needle Tubethickness two adjacent size Number Slit length (mm) (μm) slits (μm)(gauge) of slits Pattern (approximately) (approximately) (approximately)21 (0.8 mm 5 A  10 (type 1A) and 100 630 OD) 15 (type 2A) B 6.5 (type B)

Tubes will be modified in three different patterns (A, B, and C), asshown in FIGS. 2A-2C, respectively, to produce elastic sheaths 40 of thesubject invention. Patterns A and B will produce sheaths 40 with 10 mmand 15 mm long slits 20, respectively. In structure A, the modifiedballoon 30 will be located at one end of the slits 20 (towards thecatheter tip); whereas, in structure B, the balloon 30 will be locatedin the middle along the length of the slits 20. The operation of thedevice with structure A is “one way” such that, after being passedthrough the thrombus, the cage structure is deployed and then pulledback through the thrombus, disrupting the thrombus and capturingthrombotic debris. Unlike structure A, structures B and C have doublecage structures, which means that they function to disrupt and capturethrombus both when pushed and pulled through the occluded region of thevessel. Therefore, it is expected that the double cage structure willhave an advantage in grabbing more thrombus, compared to the single cagestructure. As described previously, longitudinal slits 20 will be madeunder a microscope using sharp surgical blade of about 10 micron tipsize. The total number of longitudinal slits 20 in each elastic sheath40 will be 5.

Example 5 Mechanical Testing of an Elastic Sheath

All mechanical testing will be performed using an INSTRON model 4301(INSTRON Corporation, Canton, Mass.). Using an appropriate load cell(e.g., tension/compression 250 gm load cell, INSTRON model: type 00), acomplete stress-strain profile for both modified and unmodified tubingwill be generated. By this measurement, the mechanical characteristicsof all three structures, A, B and C, will be compared directly.

Flexibility and maneuverability testing are useful to predict thefeasibility of navigating the device through the tortuous intracranialvasculature system in the brain. A three-point bend test will beconducted. A bend test fixture and an “S” hook for the bend test will bedesigned and constructed. Thin tubes will likely kink while performingthe bend test. In order to overcome this problem, compliant (highlyflexible) silicone rods of an appropriate size will be made and used assubstrate for the tube. Once the tube is mounted over the rod, it willnot kink while performing the bend test. Approximately 0.8 mm ODsilicone rods will be made from two-component platinum cure SILASTIC T2(DOW CORNING, Midland, Mich.) mold making rubber. Appropriately sized(e.g., about 0.8 mm ID) melting point glass capillary tubes (KIMAX-51borosilicate glass from KIMBLE-KONTES, Vineland, N.J.) will be used as amold substrate. Once cured inside the capillary tube, the silicone rodswill be removed from the mold by dissolving the glass in hydrofluoricacid.

The measurement of the string tear strength will be important in orderto prevent breaking of the strings in the cage structure during thethrombus retrieval process. We will first mount the modified tube on anappropriate rigid rod (stainless steel needle), and then both ends ofthe tube will be fixed to the rod by tying with non-stretchable fiber.Using an INSTRON setup, each string will be pulled with respect to therest until it breaks. A stress versus displacement plot will begenerated for the comparison of string strengths of three differentstructures.

Example 6 In Vitro Performance Testing of the Thrombectomy Device in aMiddle Carotid Artery (MCA) Model

SENTRY balloon catheters (150 cm long) will be purchased from BOSTONSCIENTIFIC-TARGET, Fremont, Calif. The balloon diameter and the balloonlength are 3.5 mm and 15 mm, respectively, when inflated. The diameterof the catheter at the balloon is 0.86 mm when un-inflated. The balloonportion of the catheter will be modified to create balloon types A and Bby constraining it at both ends into a 2 mm long balloon in the middle,as shown in FIGS. 2A and 2B. Balloon type C (FIG. 2C) will be madesimilarly as type A and B with the exception that, in type C, theballoon will be further split into two halves by constraining the middleportion of the balloon. This will be done by wrapping aroundstretchable, segmented polyurethane fiber. Prior to wrapping, the fiberwill be pre-stretched about 100% of its original length. The balloonmodification steps will be carried out under a microscope. When pressureis applied by injecting saline, only the unobstructed balloon portionwill inflate, as shown in FIGS. 3A-3C. Mechanical testing of themodified balloon catheter will involve measurement of the balloondiameter increase with respect to the saline pressure to determine theoptimum inflation pressure. Mechanical testing on these modifiedballoons will then be performed. A plot will be constructed showing theincrease of the balloon diameter with respect to the increase of thesaline pressure. This plot will facilitate the determination of optimumsaline pressures for a desired balloon size.

Both the modified balloon catheter and the modified tube will bere-inspected under a microscope before the final assembling. Themodified polymer tube will then be swelled by immersing it in anappropriate solvent as described before. Swelling of approximately 30%of its original size would be sufficient to slip it over the modifiedballoon. The ID of the tube will purposely be made smaller than the ODof the balloon portion of the catheter. Once dried under the vacuum, theelastomeric tubing will capture the modified balloon firmly. Schematicrepresentation of the device is shown in FIGS. 4A-4C. In order to securethe thrombus inside the cage structure, a “spider-web” like pattern canbe made near the balloon of the device, covering about 50% of the tubelength, for example, as shown in FIG. 5. Polymer solution (same as thetube material) will be directly applied in the form of a fine fiber ontothe inflated device in such a way that it will connect the elastomericstrings.

The mechanical testing will be performed using an Instron setup asdescribed earlier in the preliminary study section. The flexibilitytesting of the device will be performed by a three point bend test. Acalibration curve will be generated showing maximum cage diameter withrespect to the saline pressure. This experiment will help for in vitroand in vivo testing of the device.

A polypropylene tube (PP) of 2.50 mm ID will be used for making themodel of the tortuous MCA. This type of tube may kink while bending itto give the tortuous shape. To overcome this problem, an appropriatesize copper wire will be inserted inside the PP tube first to give theright shape to the tube. Translucent silicone glue (SILASTIC T2 from DOWCORNING) will be applied over the PP tube and then it will be heattreated. Once cured, silicone oil will be injected into the tube to makethe tube interior slippery. Then the structure will be straightened andthe copper wire support will be removed. Once released, the tube willreturn to its tortuous shape. Silicone over-coating should reinforce andretain the structure. It will then be cleaned and installed as shown inFIG. 7A.

Clots will be made directly from rabbit blood. The plastic MCA modelwill be marked A, B, C, D and E, as shown in FIG. 7A, which willrepresent different locations of the MCA. The tube will then be cut ateach location to attach a clot holder. The clot holder will be adetachable silicone pouch with two openings, as shown in FIG. 7B. Bothopenings of the holder will be attached to the model through plasticfittings. This pouch will then be filled with condensed clot (the clotcondensation will be done by centrifugation). Before operation of thedevice, the model will be bathed with saline solution. All locations,from A through E, will be tested with the device to evaluate the deviceperformance at each location. The feedback from the in vitro testingwill help for the further development of the device. A repeatedredesigning and remanufacturing process will be carried out to optimizethe device performance for three different cage patterns (A, B and C).This investigation will provide information on the best polymer material(out of four different materials) for each cage pattern.

Example 7 In Vivo Performance Testing of the Thrombectomy Device in aRabbit Kidney Occlusion Model

A rabbit kidney occlusion model closely mimics the MCA in humans (interms of the lumen size) will be utilized. Prior to the surgicalprocedure, the animal will be sedated with acetylpromazine (0.5-2.0mg/kg SQ or IM) and 0.5 ml of blood will be drawn from the centralauricular artery and allowed to coagulate in a 3 ml blood collectiontube with a wire for one hour at 37° C. This autologous thrombus will beused for creation of the thromboembolic occlusion. The animal will thenbe weighed to determine proper injectable anesthetic doses, and placedunder general anesthesia. General anesthesia will be induced with KAX(0.6 ml/kg), a mixture of 10 ml ketamine HCl (PHOENIX PHARMACEUTICALS,100 mg/kg), 2.0 ml acepromazine maleate (PHOENIX PHARMACEUTICALS, 10mg/kg), and 1.5 ml xylazine (PHOENIX PHARMACEUTICALS, 100 mg/kg).

Following sufficient sedation, the animal will be intubated and attachedto a ventilator providing an oxygen mixture (21% oxygen USP, 79%nitrogen). The surgical site will then be shaved, prepped and draped ina sterile fashion using 3 cycles of surgical scrub andalcohol/chlorhexidine rinse. The level of anesthesia will be monitoredby heart rate, respiration rate, temperature, animal movement, pupillarysize, toe pinch reflex, blinking reflex, fluid balance tearing, andsalivation. Additional doses of KAX (0.3 ml/kg) will be given tomaintain general anesthesia. An incision will be made in the hindlimb ofthe rabbit to expose the femoral artery for catheterization. A slit willbe cut in the artery with micro-scissors and a 4F introducer sheath willbe placed into the femoral artery and secured in place with a 4.0 silksuture. A 3F angiographic catheter and a guidewire will then be advancedwith fluoroscopic guidance towards the right kidney untilcatheterization of the renal artery is achieved (1.5-3.5 mm diameter).Digital subtraction angiography will be performed to confirm properplacement of the catheter (FIG. 8).

After the previously obtained autologous thrombus has matured for 1hour, it will be cut into 2 sections and a section will be placed into a0.9% saline filled syringe for embolization. The thrombus segment andsaline will then be injected into the lower branch of the right renalartery. Without moving the catheter, the second clot segment will beinjected. Successful thromboembolism of the renal artery will beconfirmed with angiography (FIG. 9). The left renal artery will then becatheterized with the same technique. The same procedure as describedabove will be repeated in the left renal artery. All of the animals willremain under general anesthesia for 30 minutes after thrombus injection,but before initiating any treatment.

Final angiography will be performed bilaterally 4 hours after clotinjection to determine recanalization status and will be graded with theTIMI (Thrombosis in Myocardial Infarction) score, which is a commonlyused system for grading recanalization. The animal will be euthanizedwith an overdose of sodium pentobarbital. The kidneys will be surgicallyremoved, sliced into 5 mm sections and allowed to soak in TTC stain for30 minutes. The specimens will then be digitally photographed (FIG. 10)and the infarction percent of each kidney will be calculated.

It should be understood that the examples and embodiments describedherein are for illustrative purposes only and that various modificationsor changes in light thereof will be suggested to persons skilled in theart and are to be included within the spirit and purview of thisapplication.

1. A device for occlusion removal and/or disruption comprising: a rod;an elastic sheath that ensheaths a segment of said rod, wherein saidsheath has a plurality of slits; and means for expanding said elasticsheath, and wherein said elastic sheath is displaced from said segmentof said rod when said expansion means is activated, and wherein said rodand said elastic sheath cooperate to form a compartment when saidexpansion means is activated.
 2. The device of claim 1, wherein saidexpansion means comprises an expandable balloon, wherein at least aportion of said expandable balloon is covered by said elastic sheath. 3.The device of claim 1, wherein said plurality of slits arelongitudinally arranged around at least a portion of the circumferenceof said elastic sheath, and wherein each slit is separated from adjacentslits by a longitudinal band of elastic material.
 4. The device of claim3, wherein said longitudinal bands are cross-linked with a plurality oflateral bands that bridge said longitudinal slits, thereby forming amesh.
 5. The device of claim 2, wherein said expandable ballooncomprises at least one radially constrained portion and at least oneradially unconstrained portion.
 6. The device of claim 5, wherein whenpressure is applied to said expandable balloon, said at least oneradially unconstrained portion expands to form at least one sphere orspheroid shape.
 7. The device of claim 6, wherein said at least oneradially constrained portion is constrained with a fiber that is wrappedaround said at least one radially constrained portion.
 8. The device ofclaim 6, wherein the compartment is substantially conical in shape. 9.The device of claim 1, wherein the elastic sheath comprises a flexiblepolymer tube.
 10. The device of claim 1, wherein the elastic sheathcomprises a thermoplastic elastomer.
 11. The device of claim 1, whereinthe elastic sheath comprises a flexible polymer selected from the groupconsisting of silicone, polyurethane, silicone-polyurethane copolymer,and styrene-ethylene-butylene-styrene (copolymer).
 12. The device ofclaim 1, wherein said device is at least partially composed of animageable material.